Total synthesis of siphonazole and its O-methyl derivative, structurally unusual bis-oxazole natural products.
The details of the first syntheses of the unusual bis-oxazole natural products siphonazole and its O-methyl derivative are reported. The cinnamyl substituted oxazole was constructed using diazocarbonyl chemistry, whereby the cinnamamide was reacted with the rhodium carbene derived from methyl 2-diazo-3-oxobutanoate to give a beta-ketoamide that was cyclodehydrated to the corresponding oxazole-4-ester. Reduction to the corresponding aldehyde was followed by coupling with a zinc reagent derived from methyl 2-iodomethyl-5-methyloxazole-4-carboxylate, also prepared using rhodium carbene chemistry, to give, after oxidation of the resulting secondary alcohol, the desired bis-oxazole ketone. The syntheses were completed by hydrolysis of the ester and coupling of the 2,4-pentadienylamine side chain.
Linder
Jörg
J
School of Chemistry, University of Nottingham, University Park, Nottingham, UK NG7 2RD.
Blake
Alexander J
AJ
Moody
Christopher J
CJ
D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry*
D001688:Biological Products; D010080:Oxazoles; C520719:siphonazole